The first major step of nucleophilic radiofluorination is drying the aqueous [18F] fluoride which is commonly performed in the presence of a phase-transfer catalyst under azeotropic evaporation conditions (Coenen et al., J. Labelled Compd. Radiopharm., 1986, vol. 23, pgs. 455-467). [18F] fluoride dissolved in the target water is often adsorbed on an anion exchange resin and eluted, for example, with a potassium carbonate solution wherein the eluting carbonate solution contains the cryptand which complexes the fluoride to form the cryptate complex. (Schlyer et al., Appl. Radiat. Isot., 1990, vol. 40, pgs. 1-6). The subsequent azeotropic drying of a cryptate, which is a cage-like agent, is generally performed under reduced pressure which requires additional technical equipment. One cryptand that is available commercially is 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo [8,8,8] hexacosan, with the tradename Kryptofix 222. A cryptand is a cage-like agent that has three ether ribs joining the nitrogens at each end. Alkali metals can be held very strongly inside the cage. Cryptands and other macrocyclic complexing agents are known as the “crown” ethers that consist of large puckered rings held together by several ether linkages.
It has been noted that such a complexing agent should be adsorbed at the site of the electrodes and furthermore, these agents could furnish the electrochemist with a useful cationic adsorbate, with a negative desorption potential. Pospisil et al. has demonstrated that a crown complex of T1+ is adsorbed at a dropping mercury electrode. (Pospisil et al., J. Electroanal. Chem., 1973, vol. 46, pg. 203). Pospisil et al. and Britz et al. demonstrated the use of complex adsorption in the electrosynthesis of tetraethyl lead. (Britz et al., Electrochem. Acta, 1968, vol. 13, pg. 347).
Another useful property of alkali metal ion complexes with cryptands is that the complex is reduced at mercury at much more negative potentials than the uncomplexed ion. This has been examined by Peter and Gross who found a potential shift for the K+ complex of about −1V. (Peter et al., J. Electroanal. Chem., 1974, vol. 53. pg. 307).
In Hamacher et al., an electrochemical recovery of n.c.a. [18F] fluoride in dipolar aprotic solvents and solutions of phase transfer catalyst is discussed. (Hamacher et al., Appl. Radiat. Isot., 2002, vol. 56, pgs. 519-523). This disclosed recovery process allows the use of a specifically designed electrochemical cell as a reaction vessel for n.c.a. nucleophilic 18F-fluorinations subsequent to [18F] fluoride deposition. In other words, Hamacher et al. uses an electrochemical cell within a chamber that comprises two electrodes across which an electric field is applied. The [18F] fluoride anions are adsorbed onto the surface of the anode while the [18O] water is flushed from the electrode chamber. Hamacher et al. further conclude that a specifically designed electrochemical cell is generally useful for n.c.a. nucleophilic 18F-radiotracer syntheses. Especially in the case of base labeled products like butyrophenones, the electrochemical cell allows cryptate catalyzed 18F-fluorination in the presence of weak basic, less nucleophilic salts like potassium oxalate or triflate.
It is important to note here that a cryptand is a phase-transfer agent used to improve the solubility of [18F] fluoride in non-aqueous environments and that a [18F] fluorinated species defined herein comprises chemical or biological [18F] fluorinated compounds.
There is a need for creating an electrochemical radio-labelling approach that can increase the yield of a [18F] fluorinated species by up to 20% more than previous methods from the use of a electrochemical cell whereby a conducting polymer-modified electrode is combined with an anhydrous solvent where the polymer electrode is switched to a reducing potential and all retained anions are expelled from the polymer matrix and thereafter a phase transferring agent is combined with said anhydrous solvent. Moreover, the potential needed to oxidise the polymer will only be ca. +2 V (versus, for example, a silver-silver chloride reference electrode). The positive charge density at the polymer electrode will drive fluoride ions towards the oxidised polymer electrode far more than if it was an unmodified electrode. In other words, a lower potential is preferred to achieve the same level of fluoride adsorption. Furthermore, the modifying polymer layer masks the electrode surface and so precursors are unlikely to be degraded at the electrode surface.
Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.